Tuberculous Lymphadenitis: Mantoux test and cytokines profiles as markers of disease and healing

Abstract

Mycobacterial disease due to Mycobacterium tuberculosis remains a major public health problem worldwide. Directly observed therapy, short course (DOTS) helped to control the spread of tuberculosis but additional threats are posed by the HIV pandemic and multi-drug resistance. Tuberculosis (TB) is a relatively new disease in the Sudan, it was not known in this country until the end of the 19th century. Since then, data accumulated showing that the incidence of both pulmonary and extra pulmonary tuberculosis in Sudan is raising. The only currently available vaccine against tuberculosis BCG provides variable protection in different settings. There are no accurate measurable immunological markers that correlate with disease and healing/protection in mycobacterial diseases. Patients with tuberculous lymphadenitis, although have the disease, they are in better health compared to those with pulmonary TB. Study of this group of patients will hopefully help in identifying markers of immunity. Aim: To determine accurate measurable immunological markers of disease and healing of tuberculous lymphadenitis infection. Methods: Following informed consent, patients with tuberculous lymphadenitis and comparator groups (pulmonary tuberculosis and healthy individuals) were enrolled in the study. For every study subject, hematological profiles and Mantoux test were performed. IFN-γ and IL10 were estimated in the PBMCs culture supernatant. Patients with tuberculous lymphadenitis were 7 followed closely throughout the study period (6 months) and hematological profiles, Mantoux test and cytokine estimations were performed again at the end of treatment. Results: Thirty six patients with FNAC cytomorphological diagnosis of tuberculous lymphadenitis (TBLN), 40 patients with pulmonary disease and 20 healthy volunteers were enrolled in the study. The ages and the hematological profiles of the study groups were found to be comparable. Mantoux test was found to be reactive in 100% TBLN patients (36/36) and remained so at cure and it was found to be significantly associated with higher levels of IFN-γ (p=0.01). Only about a third of patients with pulmonary disease were reactive in the Mantoux test. High IFN-γ and IL- 10 levels were detected in all patients with tuberculous lymphadenitis at diagnosis (disease). At the end of the treatment (healing), IFN-γ increased significantly compared with its levels at diagnosis (p=0.0001), whereas the levels of IL-10 decreased significantly compared to the level at diagnosis (disease) (p= 0.000). Patients with pulmonary disease had significantly high levels of IL-10. There was no significant difference in the levels of IL-10 in healthy controls who had reactive Mantoux test and those with treated tuberculous lymphadenitis (p=0.7).